Unraveling the complexity of anti-doping analysis: reassessing meldonium detection and doping verdicts in a case study.

BACKGROUND: The precision and accuracy of mass spectrometry (MS) made it a fundamental tool in anti-doping analysis. High-resolution (HR) mass spectrometers significantly improved compound identification. This study systematically analyzes data from an athlete (Subject 1) who tested positive for meldonium and compares it with data from a healthy volunteer (Subject 2) to examine the correctness of the doping verdict. CASE PRESENTATION: The documentation related to Subject 1 was thoroughly processed and analyzed. A study involving a volunteer (Subject 2) replicated Subject 1 regimen and urine sample collection for data alignment with anti-doping results, with Subject 2 reporting not using meldonium. The anti-doping agency's analysis of Subject 1 showed the presence of meldonium at a concentration close to the established cut-off level. However, a closer examination revealed that one specific ion, crucial for meldonium identification, was absent from the mass spectra. Analyzing Subject 2 data, using the same methodology, the absence of the specific ion was confirmed, even though the volunteer did not consume meldonium. The European directive and the method that was validated and cited by the anti-doping agency identified meldonium on at least four specific ions, whereas the anti-doping analysis used only three ions. This discrepancy compromises the specificity of meldonium identification. CONCLUSIONS: To enhance the analytical methodology, two strategic interventions are suggested: adjusting the meldonium cut-off value and expanding the analysis to include meldonium metabolites. By addressing these avenues, the precision of meldonium detection and doping verdicts can be improved. In conclusion, this study challenges the anti-doping agency's verdict and prompts a reevaluation of meldonium detection methodologies in anti-doping measures.

Typical CT findings of COVID-19 pneumonia in patients presenting with repetitive negative RT-PCR.

Multiple polymerase chain reaction (RT-PCR) is considered the gold standard diagnostic investigation for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, false negative multiple polymerase chain reaction (RT-PCR) results can be diagnostically challenging. We report three patients with history of fever and different clinical signs. During the height of the pandemic in Italy (March to May 2020), these patients underwent chest computed tomography (CT) scans that showed lung alterations typical of COVID-19 with multiple negative RT-PCR tests and positive serology for SARS-CoV-2. Two of the three patients showed residual pneumonia on CT after the onset of the first clinical signs. One patient presented with diarrhoea without respiratory symptoms. These cases suggest that in the COVID-19 pandemic period, to provide an earlier specific treatment in patients with positive serology, a chest CT scan can be useful in those presenting with a fever or a history of fever associated with persistent mild respiratory symptoms or with abdominal complaints despite repeated negative RT-PCR results.

A prospective longitudinal study on visuo-cognitive development in Dravet syndrome: Is there a "dorsal stream vulnerability"?

A group of five DS patients whose first development was already reported were longitudinally followed up till the scholar age. Beside the general and epileptic clinical evolution, visual and cognitive functions were investigated in order to define their trajectory and possibly provide information about mechanisms of cognitive decline as well as to improve prognosis and tertiary prevention. Neuropsychological assessment was performed with a test battery investigating the development of visual function that progressively integrates into extrastriate components and higher cognitive skills (global form and motion coherence, stereopsis, crowding cards, ABCDEFV battery, general intelligence and specific cognitive tests). Main results showed a fall in visuo-motor items including global motion coherence and specific cognitive skills, presenting a continuity of the visual function deterioration extended from basic abilities to visuo-motor dorsal pathway skills. Moreover, a case whose previous visual and cognitive functions had been in the normal range began showing a visual deterioration with increasing age, followed by the cognitive decline; that prevents from excluding in early ages a poor development in presence of a normal visual function. A dorsal stream vulnerability seems thus shown in this sample of DS patients, like in other genetic syndromes (Williams, Prader Willi. fragile-X), providing new information about mechanisms underlying cognitive decline and suggesting a possible strategy to improve their neuropsychological outcome. Larger cohorts may confirm whether these findings are part of a specific pattern of DS neuropsychological phenotype.

Four-year clinical and neuroradiological follow-up of a papillary tumor of the pineal region.

Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years' clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.

Safety and feasibility of the adjunct of local chemotherapy with biodegradable carmustine (BCNU) wafers to the standard multimodal approach to high grade gliomas at first diagnosis.

AIM: Among physicians there is still a reluctant attitude in the employment of combined treatment with surgery and intraoperative placement of carmustina 7.7 mg wafers (Gliadel®), followed by standard adjuvant treatment with radiotherapy and concomitant and subsequent chemiotherapy with temozolomide (TMZ), for supratentorial high grade gliomas at first diagnosis. To determine the safety and feasibility of this multimodality sequential adjuvant therapy, we reviewed our single-institution experience, in the light to provide more insights on this continuous multi-stage chemotherapy approach to such a challenging disease as glioblastoma multiforme. METHODS: From February 2006 to January 2008, 32 patients were treated at our institution for cerebral supratentorial high grade glioma with surgery and intraoperative placement of carmustine wafers. No postsurgical complications could be observed. After a median time of 4,8 weeks all patients began adjuvant concomitant radiotherapy with a mean of 60 Gy and TMZ chemotherapy 75 mg/m2 during which weekly hematologic assessments were performed. After 3 to 6 weeks patients commenced adjuvant TMZ, administered 5 days every 28, 200 mg/m2 for not less than 12 cycles. A contrast-enhanced magnetic resonance imaging (MRI) was routinely performed. Median follow-up after surgery was of 6.5 months, ranging from 4 to 23 months. RESULTS: The mean presurgical KPS was of 80 (range: from 60 to 100), and it remained unmodified after adjuvant therapies even at suspension of steroids. In 4 cases there was a radiologic evidence of progression of the disease and the necessity of steroids, with a progression-free survival (PFS) of 6, 8, 9,5 and 13,6 months. One case died 14 months after first operation. All other patients are still alive. CONCLUSION: The integration of local chemiotherapy with carmustine wafers and the standard adjuvant regimen with radiotherapy and concomitant chemiotherapy appears to be safe and feasible, without any adjunctive complication. Promising results on the efficacy require more follow up to be quantified.

Visual function in Noonan and LEOPARD syndrome.

The aim of the study was to assess various aspects of visual and visuoperceptual function in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) with mutations affecting the PTPN11, SOS1 and RAF1 genes. Twenty-four patients were assessed with a battery of tests assessing visual function including ophthalmological and orthoptic evaluation and age appropriate behavioural visual tests, including measures of crowding acuity (Cambridge crowding cards), and stereopsis (TNO test). Twenty-one subjects were also assessed with the visuo-motor integration (VMI) test. Twenty of the 24 patients (83%) had abnormalities of visual function on at least one of the tests used to assess visual function or on ophthalmological examination, and 7 of 21 (33%) also had abnormalities on VMI. Ocular movements and stereopsis were most frequently abnormal (50% and 79%, respectively). Our results suggest that visual and visuoperceptual abilities are commonly impaired in patients with Noonan and LEOPARD syndrome and they are probably related to a multifactorial etiology.

Chronic expanding intracerebral hematoma treated by mini-invasive ultrasonography-guided needle aspiration.

Chronic expanding intracerebral hematoma (CEIH) is a rare cerebrovascular disease that behaves as a slowly expanding lesion with a gradual onset of progressive neurological deficit or recurrent seizures. The etiology of the CEIH is still not clear. Even if about a half of these lesions are associated with vascular malformations, the remaining cases are post-traumatic, associated with coagulative disorders or are cryptogenic. Treatment of these lesions is controversary: while some neurosurgeons remove the hematoma with its capsule, others prefer to wait and observe it if the patient is neurologically stable. We discuss the opportunity of treating selected patients bearing a CEIH by means of ultrasonography(US)-guided aspiration in selected patients. A 42-year-old hepatopathic man with coagulation disorders was referred to us with a 2-month history of progressive right-sided weakness, speech disorders and difficulty in swallowing solid foods. Radiological findings supported a CEIH with a thin surrounding capsule. The patient underwent to US-guided aspiration of the lesion with a complete resolution of the hematoma, confirmed intraoperatively by real-time US-control and postoperatively by early and long term neuroradiological controls. US-guided aspiration is a low cost, not time consuming technique, that allows an intraoperative real-time control of the lesion and seems to be an effective alternative to open surgery in cases of CEIHs with a thin capsule.

Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature.

Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet.

Central nervous system mesenchymal chondrosarcoma.

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

Multiple sclerosis and gliomas. Clinical remarks on 10 cases and critical review of the literature.

The association between multiple sclerosis and tumours of the central nervous system is unusual. The authors analyzed the clinico-pathological elements of the correlation. The pertinent literature on this subject is critically reviewed. Ten cases of patients with an history of multiple sclerosis for more than 15 years and a clinical and radiological evidence of brain tumour were submitted to surgery in order to remove the lesion and/or to chemo- and radiotherapy. The various aspects of the association were studied in detail. A patient with multiple sclerosis, particularly with atypical symptoms, should be evaluated by an annual MRI investigation with intravenous paramagnetic contrast medium. The diagnostic work-up should be: clinical and radiological assessment; MRI in the event of atypical symptoms; Sstereotactic or neuronavigation-aided biopsy in any suspected lesions. Patients with multiple sclerosis and glioma present survival times identical to those observed in patients not suffering from multiple sclerosis. The coexistence of multiple sclerosis and brain tumours does not seem to influence the clinical evolution of either of these pathologies. We believe that it is important to achieve an early diagnosis of brain tumour in such patients with a clinical and neuroradiological follow up, so that they can be treated promptly.

Treatment of glioblastoma multiforme in the elderly in functionally non-critical areas. Clinical remarks on 22 patients.

The aim of this study was to evaluate the efficacy of multimodality treatment of glioblastoma multiforme in the elderly. Although several studies report a poor outcome in elderly patients with glioblastoma, in the light of our experience, treatment of elderly patients with glioblastoma in non-critical areas and Karnofsky Performance Status > 60 should be just as aggressive as in younger patients.